AGT基因型对贝那普利降压疗效的影响

The AGT genotype affects the antihypertensive effects of benazepril

目的研究原发性高血压(EH)患者的血管紧张素原(AGT)基因M235T多态性与贝那普利降压疗效的相关性。方法251例EH患者口服贝那普利10～20mg/d,进行为期6周的降压治疗。用聚合酶链反应(PCR)和限制性酶切方法检测所有患者的AGT基因M235T多态性,按MM、MT和TT三种基因型分组。治疗前后及治疗过程中对患者的收缩压(SBP)和舒张压(DBP)等进行监测,以比较不同基因型患者之间的降压疗效。结果基因型为MM、MT及TT者分别为23例(9.2%)、104例(41.4%)和124例(49.4%);在251例患者中,MM、MT及TT三组患者间治疗后SBP和DBP的降幅差异无统计学意义(P>0.05);按年龄分层进行的亚组分析显示:在≥60岁的老年亚组中,治疗后MM、MT及TT三组患者DBP的降幅分别为(14.8±4.8)mmHg,(7.9±7.7)mmHg和(9.8±6.4)mmHg(P=0.034),MM较MT和TT组的DBP降幅大。结论本研究显示,老年(≥60岁)EH患者的AGTM235T多态性与贝那普利降压疗效相关,提示特定的基因多态性可能会影响某些降压药物的疗效。

Objective To investigate the association between M235T variant of angiotensinogen （AGT） gene and the blood pressure response to benazepril in a hypertensive cohort. Methods Benazepril （10 -20 mg/day） was administered for 6 weeks to 251 essential hypertensives. Polymerase chain reaction （PCR） combined with restriction enzyme digestion was used to detect the polymorphism and the patients were classified as MM, MT or TT genotype. The changes in systolic and diastolic blood pressure （ SBP and DBP） were analyzed for association with genotypes at the AGT gene locus. Results The MM genotype was observed in 23 patients （9. 2% ）, the MT genotype in 104 patients （41.4%） and the TT genotype in 124 patients （49.4%）. There was no association between these polymorphisms and the blood pressure responses in the total 251 patients. But based on the analysis stratified by age, the association between these polymorphism and the DBP responses was found in the old patients （≥ 60 years old ） subgroup, the reduction in DBP was significantly greater in patients carrying the MM compared to MT or TT genotypes （14.8±4.8 mm Hg vs. 7.9 ±7.7 mm Hg or 9.8 ±6.4 mm Hg respectively; ANOVA, P=0.034）. Conclusion The M235T polymorphism of the AGT gene was shown to influence the responses to benazepril in old hypertensive patients （≥ 60 years old ）. Thus, specific genotypes might predict the response to specific antihypertensive treatment.